ALBERT

Description: Introduction Predicting treatment outcome of acute leukemia has been an important issue. Many factors have been elucidated. We evaluated the impact of donor's availability on treatment outcome including mortality in patients with acute lymphoblastic leukemia (ALL). Methods A total of 294 patients with ALL were evaluated after receiving chemotherapy between year 2001 and July 2014 at our center. Patients were assessed for the need of hematopoietic stem cell transplants (HSCT), availability of HLA sibling match donor and the impact on overall outcome. Indications for transplantation were defined as (1) WBC-〉100,000 for T-ALL, 〉30 for B-ALL with, (2) cytogenetic abnormalities of t(9:22), (4:11) or (1:19), (3) relapse or primary refractory disease or (4) MRD positivity. Patients were divided into 3 categories, group A with an indication for HSCT and available donor (HSCT+/D+), group B with HSCT indication but no available donor (HSCT+/D-) and group C with no indication for HSCT regardless of donor status (HSCT-). Results The median age was 20 (14-63 years). 95 (32%) were female while 198 (68%) were male. 276 (86%) patients were newly diagnosed while 18 (14%) were relapsed. Immuno-phenotype was B for 191 (65%), T for 91 (31%) versus mixed lineage for 12 (4%). 33 (11%) patients were positive for Philadelphia chromosome. Median WBC at diagnosis was 23.2X109/L CNS involvement was positive in 26 (8%) patients. With a median follow-up of 60 months for survivors (range 2 to 116.5 months), 148 (50%) patients showed HSCT+/D+, HSCT+/D- in 79 (27%) and HSCT- in 67 (23%) patients. the 5-year OS for HSCT+/D-, HSCT+/D+ and HSCT- were 29%, 57% and 55% (p value

Description: Introduction: Induction with 3+7 has been standard practice in acute myeloid leukemia (AML) for over 40 years. Addition of a 3rd agent or use of high dose Ara-C has been reported to show better CR rates, but this has not demonstrated a consistent improvement in overall survival. We have consistently used induction with idarubicin, cytarabine 100mg/m2 /day for 7 days and etoposide at 100mg/m2 in young patients, omitting etoposide for suspected secondary AML or AML with myelodysplasia related features, or in those in whom excess toxicity is suspected. Methods: All patients wholly treated for newly diagnosed AML were identified from the prospective institutional AML database. Patients were treated with either ICE (Idarubicin 12mg/m2 day 1-3, Ara-C 100mg/m2 day 1-7, Etoposide 100mg/m2 d1-3) or the same doses of idarubicin and Ara-C without etoposide (3+7). The latter was given in patients with dysplastic features or secondary AML or where there were concerns of toxicity. Results: We Identified 116 patients who received one of the 2 induction regimen between 2005 and 2013. 90 patients received ICE and 26 patients received 3+7. Median ages in the groups were 29y (14-56) and 37y (15-58), respectively. Cytogenetics by ELN classification were similarly distributed between the ICE and 3+7 groups, with favourable/intermediate/adverse cytogenetics comprising 22%/46%/26% and 23% / 38% / 26%, respectively. 21/90 (23%) in the ICE group had 〉5% blasts in a day 14 bone marrow vs 7/26 (27%) in the 3+7 cohort. There was no significant difference in the CR/CRi rate between ICE (82%) and 3 + 7 (77%) groups. The death in aplasia rate was similar at 3.3% and 3.8%, respectively. 65/90 (72%) and 14/26 (54%) of patients received a transplant in CR1 or beyond in the ICE and 3+7 groups, respectively. Leukemia free survival was 40% (SE 10%) and 40% (SE 5%) in both cohorts (Fig.1). Overall survival at 5 years for ICE and 3+7 were 57% (SE 6%) and 49 % (SE 13%), p=0.69 (Fig.2). Conclusion: Our experience in young adults, albeit retrospective, confirms findings of larger studies that demonstrate that addition of etoposide to induction does not appear to improve remission rates significantly or improve survival. In order to improve remission rates in younger adults, FLAG-Ida or other regimens consisting of high dose Ara-C and/or novel agents may provide more tangible improvements in remission rates, although strategies that translate these into better overall survival remain elusive and this should be the target of further prospective trials. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4894 Background: Pretreatment karyotypes of leukemic cells provide the core for risk-stratification schemes in acute myeloid leukemia (AML) and cytogenetic abnormalities are well established as the strongest prognostic factor for response to therapy and for survival in AML patients. Several cytogenetic risk classifications have been built to stratify AML patients. Only the recent European Leukemia Net (ELN) recommendations by an international panel proposed a new standardized cytogenetic reporting system for AML. More importantly, few studies attempted so far to validate the ELN requirements for risk assessment in AML patients treated with allogeneic hematopoietic stem cell transplantation (HSCT). We investigated whether our series of adult AML patients treated with HSCT could validate the ELN classification criteria. We also assessed the prognostic value of this new risk stratification scheme. Methods: ELN cytogenetic reporting criteria were applied to a series of 110 adult AML patients from a single institution in the Middle East for whom complete cytogenetic data from pretreatment leukemic marrow were available and patients were assigned to the proposed cytogenetic risk subgroups, accordingly. We compared outcome for the different prognostic subgroups. Parameters analyzed were overall survival (OS) and event-free survival (EFS). Our AML group included 62 (56%) patients treated in their first remission (CR1), while most non-CR1 AML patients were treated with HSCT in CR2. The median age of all patients was 25 years (range: 14–57). Results: The patient group included 32 (29%) patients with favorable risk, 60 (55%) in the intermediate-risk group, and 18 (16%) in the adverse-risk group. When all the three groups were considered, there was significant difference in overall survival (OS) (P=0.007) and event-free survival (EFS) (P=0.007). However, there was no significant difference between our favorable-risk group and the intermediate-risk group. This is most likely due to selection bias in the favorable group (e.g. CD56 expression and other unfavorable markers). The adverse-risk group had significantly (P=0.002) shorter survival with median survival of 7.5 months vs. the intermediate-risk group where median survival has not been reached with an average follow-up of 46 months. When we attempted to consider only patients treated with HSCT in the first remission, there were too few patients in the intermediate-risk group (7 patients) for statistical evaluation. Conclusions: The ELN criteria proofed valuable in risk-stratifying our set of adult AML patients who were treated with HSCT and represent a Middle Eastern population. Our series clearly validated the ELN classification. The ELN classification needs further validation in patients treated with HSCT in first remission. Disclosures: No relevant conflicts of interest to declare.

Description: Background HLH is an under-estimated and under-reported syndrome with diverse etiologies but can cause life threatening cytopenia (s) and organ failure with very high mortality in critically ill patients. Early diagnosis and management are of paramount importance for better survival. The current HLH 2004 diagnostic criteria are not optimal to achieve such a goal. Monocytopenia is not included in the diagnostic criteria although HLH is associated with activation, mobilization of and shift of monocytes to tissues where phagocytosis occurs. Hypothesis and Goal We hypothesized that monocytopenia is expected to occur patho-physiologically in HLH and accompany other cytopenias and treatment should be associated with reversal of monocytopenia in adults with HLH associated with different diseases. Methods and subjects: This is a retrospective analysis of 20 consecutive adult patients (〉/= 16 years) with complete records diagnosed on in ICU or in-patient hematology consult service at our institution who presented with fever and cytopenia(s) between Dec. 1st and June 30th, 2016. All patients fulfilled at least 5 out of 8 HLH2004-diagnostic criteria and/or had a genetic mutation of Familial HLH. Results: A total of 20 patients (3 females) with a median age 27 y (range 16-69) with diverse diagnoses (Table 1): 10 patients had malignancies; the most common (7; 70%) were lymphomas (3 HD, 1 DLBCL, 1 Plasmablastic NHL, 1 T cell NHL and PTLPD). 3 patients had myeloid malignancies (1 MDS, 1 active AML and one after FA salvage for AML), 3 were post allo-HSCT in CR (2 cGVHD; one on Cyclosporine), 1 post-Autologous HSCT for AML in CR, 1 HLH with RAB27 mutation, 1 ITP and AIHA (Evan's) presented with portal and superior mesenteric vein thrombosis, 1 Kostman Syndrome, 1 HIV on HAART therapy, 1 MethylMalonic Acidemia (MMA) and one with Adult Onset MAS -SJIA. The triggering or Co-triggering factors were considered to be due to H1N1 in 10 (50%) patients (5 with active malignancy) as it is an epidemic in Saudi Arabia since 2009; one with CMV reactivation post Allo-HSCT, EBV in 2 (10%) (1 with PTLPD after renal transplant on CSA and 1 with HLH-RAB27 mutation), , 1 chemotherapy (Fludarabine+ AraC) triggered during extended neutropenia and sepsis, 3 patients (DLBCL, T Cell NHL, HD) presented with malignancies with HLH without known triggering factor except malignancy (Malignancy-triggered HLH). 4 patients had no known triggering factors (T cell -NHL, DLBCL and t- MDS in CR 5 years after 2-CDA therapy for HCL. All patients fulfilled at least 5 criteria out of 8 according to HLH-94/HLH 2004 guidelines' criteria as shown in table-1 including a patient with HLH with RAB27 mutation 19 (95%) patients developed monocytopenia

Description: Introduction: The use of a Myeloablative (MA) regimen followed bypost-transplantation high dose Cyclophosphamide (PT-CY) has been adopted to overcome the increased relapse risk following nonmyeloablative conditioning regimen and unmanipulated Haploidentical Bone Marrow Transplantation, in patients with high-risk hematological malignancies, with acceptable TRM and risk of GVHD. We added ATG to our Myeloablative regimen with PT-CY after noticing significant incidence of grade II-IV aGVHD with the first few cases. Here we compare the outcomes of the 12 patients who received ATG to the outcomes of the first 11 patients who were transplanted without ATG. Patients and Methods: our haploidentical program was started in 2013 as a phase I/II prospective clinical trial. After reviewing the first 11 cases enrolled on the trial (MA regimen with PT-CY, without ATG), we noticed significant incidence of high grade aGVHD (54.55%). We amended our protocol in early 2015. Rabbit ATG was added at a dose of 3 mg/kg (1.5 mg/kg day -3 and day -2) to our conditioning regimen [thiotepa (5mg/kg/day on day -8 and -7), busulfan (3.2mg/kg/day IV day-6, -5 and -4), fludarabine (50mg/m2/day on day -6, -5 and -4 )] or [TBI 1000 cGy (200cGy twice a day on days -10, -9 and one dose on day -8), fludarabine (30mg/m2/day on Days -7, -6, -5 and -4)]. Graft-versus-host disease (GVHD) prophylaxis consisted of PT-CY (50mg/kg/day) on days +3 and +5, cyclosporine (starting day +4), and mycophenolate mofetil (starting day +1). Table 1 summarizes the disease-type and disease-status at transplant. Patient characteristics were comparable at baseline between the 2 groups. Results (Table 2): We enrolled patients with high risk hematologic malignancies in need for SCT but have no matched donor (MSD, MUD). Despite the small sample size, our results showed a statistically significant difference in the rate of acute GVHD between the 2 groups (p= 0.0161) in favor of the ATG group, chronic GVHD was more frequent in the non-ATG group however the difference did not reach statistical significance probably due to the small sample size. There was no statistically-significant difference in the risk of relapse, CMV reactivation or Hemorrhagic cystitis between the 2 groups. However, there was a trend of higher relapse rate (33.3% vs 18.18%), a higher rate of Hemorrhagic cystitis (50% vs 18.18%) and a higher rate of CMV reactivation (100% vs 81.82%) in the ATG group. The cumulative incidence of TRM at day 100 was in favor of the ATG group (figure 1), with a trend toward a better DFS in these patients 6 months post-transplant (figure 2). To be noted the follow up period was shorter for the ATG group because ATG was added later on. Figure 3 shows the survival for ATG vs non ATG group. Conclusion: The use of ATG with myeloablative Haplo conditioning can significantly reduce the risk of acute GVHD and early TRM. We have seen more relapses, higher rate of CMV reactivation, and hemorrhagic cystitis with the addition of ATG but these did not reach statistical significance probably due to the small sample size. A lower dose of ATG might be the way to go to strike a careful balance and improve the outcomes of myeloablative haploidentical transplant. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 2527 Background: In contrast to most translocations affecting the MLL gene, the t(9;11) is not associated with a markedly poor prognosis. Several studies revealed a very favorable outcome in the pediatric patient group. In adult AML, the t(9;11) has also been associated with superior survival, at least compared to other 11q23 abnormalities. Therefore, 11q23 rearrangements in adult AML are now often dichotomized into t(9;11) and non-t(9;11), with the former being included in the intermediate-risk group and the latter in the adverse-risk group. The proposed European Leukemia Net (ELN) cytogenetic reporting criteria reflect this division. We investigated whether the outcome of AML patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) with t(9;11) remains significantly different from the rest of the adverse-risk cytogenetic group. Methods: Conventional cytogenetics and FISH data from diagnostic bone marrow of 110 adult AML patients treated with HSCT was reviewed and patients classified according to the recommendations of the European Leukemia Net and included 32 with favorable risk, 60 in the intermediate-risk group, and 18 in the adverse-risk group. FISH confirmed MLL rearrangement in cases with apparent 11q23 abnormalities. We compared outcome of patients with t(9;11) to the group of patients with adverse-risk cytogenetics that included all MLL-positive non-t(9;11) among other cytogenetic abnormalities classified adverse-risk. Our study included 62 (56%) patients treated in first remission (CR1), while most non-CR1 AML patients were treated with HSCT in CR2. Patients were between 14 and 57 years, with median age of 25 years. Results: Of the 110 AML patients, 9 (8%) had MLL gene rearrangement. Of these patients only 5 (4.5% of all patients) had t(9;11). When all patients with MLL rearrangement were considered, there was no significant difference between this group and the patients with adverse-risk cytogenetics in overall survival (OS) or event-free survival (EFS). In contrast, when only patients with the t(9;11) were considered, the t(9;11) patients had significantly longer OS (P=0.02) and EFS (P=0.03) as compared with patients with adverse cytogenetics including all non-t(9;11) MLL-rearranged cases. The outcome of MLL-positive non-t(9;11) patients was similar to the group with adverse-risk cytogenetics. MLL rearrangements in the non-t(9;11) group included t(4;11)(q21;q23), t(6;11)(q27;q23) and a variant t(6;11;7)(q27;q23;q11.2), as well as t(11;17)(q23;q25). The survival for patients with t(9;11) remained significantly longer even when only patients treated with HSCT in first remission were considered, although numbers were small. All five patients with t(9;11) were treated with HSCT in CR1. Conclusions: The data supports the conclusion that MLL-positive t(9;11) AML patients should be classified differently from the rest of the MLL-rearranged cases and should be considered as part of the intermediate-risk group. This classification separating the t(9;11) cases from the rest of the MLL-positive cases should be maintained even when patients are treated with allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4464 Background: Alterations of the short arm of chromosome 12, most often resulting in loss of chromosomal material, are a recurrent feature in myeloid malignancies and occur in about 5 % of cytogenetically abnormal AML. Chromosomal abnormalities of 12p in AML have been reported to be associated with a non-favorable outcome. However, it is unclear how dismal the outcome is, as AML with 12p abnormalities is variably included in the intermediate or poor prognosis groups. Moreover, the role of allogeneic hematopoietic stem cell transplantation (HSCT) on outcome of patients with 12p abnormalities is not known. We investigated whether HSCT can improve the poor survival of patients with 12p abnormalities. Method: Bone marrow conventional cytogenetic and FISH data from 110 adult AML patients was reviewed and patients were divided into three cytogenetic risk groups according to the European LeukemiaNet reporting system while separating the patients with 12p aberrations into one independent fourth group. We also compared outcome of the 12p group with to the intermediate group alone or after combining intermediate with favorable, since there was no significant difference between the favorable and the intermediate groups. The AML cohort included 62 (56%) patients treated in their first remission (CR1) while most non-CR1 AML patients were treated with HSCT in CR2. The median age of all patients was 25 years (range: 14–58). Result: Patients with 12p abnormalities were 4 (4%). Patients with 12p abnormalities had a significantly shorter overall survival (OS) (P=0.03) and event-free survival (EFS) (P=0.04). Their outcome was similar to the adverse-risk cytogenetic group, and survival was significantly shorter than in the intermediate group (P=0.02). The poor outcome was significant even when only patients treated with HSCT in first remission were considered. All four patients with 12p abnormalities were treated with HSCT in CR1. Conclusion: Although the number is small, this data suggests that 12p chromosomal changes in AML are significant adverse abnormalities, not different from complex cytogenetics, and treatment with HSCT does not change this dismal outcome. This also suggests that for patients with 12p abnormalities, alternative therapeutic approaches should be considered. Disclosures: No relevant conflicts of interest to declare.